The end of overeating
Looks like an interesting book. Nice write up in the NYT Well blog.
iPhone AT&T conspiracy theory
The recent behavior of AT&T regarding the upgrade from iPhone 3G to 3GS may shed light on how long we have to wait for a second iPhone carrier in the U.S.
No one outside of AT&T and Apple know for sure the duration of AT&T’s exclusivity. In August of last year USAToday said the contract lasts until 2010 .
My thought is that if the exclusive contract ran out at the end of 2009 or by June of 2010 then AT&T would be behaving differently right now. Instead of telling people whoose contracts expire in a year to get lost for a year they would be rolling out the red carpet to extend their contract for another 2 or 3 years.
Eventually the exclusive deal will end and an early sign of that day will be AT&T offering current customers a deal to extend their contract. AT&T’s current behavior signals that the exclusivity is here for at least a couple more years.
Myles Wolf is coming to speak at Renal Grand Rounds today
Wolf has been everywhere and is one of the premiere scientists elucidating mineral metabolism. He was the senior author on the article in the NEJM on FGF-23 and dialysis survival and the recent article on the survival advantage with phosphorous binders.
Just a quick review of FGF-23 so I’m not an idiot when this rock star nephrologist starts talking. (FYI don’t let the clean cut pic above fool you, he came to the lecture in full rock-star fashion with the long hair, groupies (supplied by Genzyme) and everything)
FGF-23 is produced by osteocytes.
Klotho seems to be a required co-factor for FGF-23, such that mice that are Klotho deficient mimic the phenotype of FGF-23 deficiency.
FGF-23 increases renal phosphorous clearance by blocking Na-Phos reabsorbtion in the proximal tubule. FGF-23 also inhibits 1-alpha-hydroxylase, decreasing 1,25 OH-vitamin D.
Some of the biology is still a mystery. The highest density of fgf-23/klotho receptors are located in the distal tubule but the biologic effects stem from the proximal tubule.
FGF-receptor and Klotho are also found in the parathyroid gland but the exact role it plays is unclear. Some data points to direct stimulation of PTH and both molecules tend to rise together but this may be due to FGF-23 surpressing 1,25 OH D and secondary increases in PTH.
Increased phosphate and 1,25 vitamin D both stimulate the production of FGF-23. [Note Wolf provided data that phosphate levels do not increases FGF-23. He proposed that it is phosphate balance that is important, his supporting data included lupron treated patients bump their phosphorous by half a point but FGF-23 doesn’t budge, I couldn’t find this article on Google]. The Phex endopeptidase cleaves and inactivates FGF-23 so that is another control factor. [Wolf also discussed iron infusions causing phosphorous wasting due to excess FGF-23 ref pubmed related search]
Here it is
Where’s my iPhone 3.0 software?
Phil told me it would be here on the 17th.
Getting another abstract (or two) ready for Renal Week 2009
We are racing the deadline for our ASN abstract. We have a great data set on geriatric patients in a structured CKD clinic. We need to define stable renal function. Our first try used the CKD stages. Our cohort is restricted to CKD 3b and 4. So stable was any patient who began and ended the study in the same CKD stage. This has been done in the literature, so there is some precedence but it doesn’t feel right to me.
Think about two participants in our study, both GFRs fall by 3 cc/min over three years, just about what the Baltimore Longitudinal Study on aging predicts. Patient A started with an eGFR of 31 mL and Patient B started with an eGFR of 33. These patients have the same clinical course and outcome but Patient A goes from 31 to 28 mL/min and hence from CKD Stage 3 to 4 while Patient B goes from an eGFR of 33 to 33 so his stage does not change.
I need a definition of stable renal function. You can help by filling this 5 question anonymous survey. We are looking
How would you define stable renal function:
Candidate A: Change in GFR less than 2 cc/min/yr (essentially 3x the average rate determined by the Baltimore Longitudinal Study on Aging).
Candidate B: Change of GFR of less than 20% from baseline to the end of the study
Candidate C: Change of less than 10 mL/min from the baseline visit
Note: baseline visit is the 1st contact with us with a GFR<45 mL/min(CKD stage 3b), we removed any patient who does not have a second eGFR < 45 at least 3 months before the initial measurement.
Dabble DB
Online endocrine textbook
This looks pretty cool.
Here is the link to the section on kidney stones written by Murray Favus. On my brief overview it looks good.
Being in the textbook business in the era of free online textbooks, UpToDate and wiki’s has got to be a world of hurt.
Renal stents for preservation of renal function with atherosclerotic renal artery stenosis
The annals has an article this week on renal stents and again they fail.
Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function
They randomized 140 patients with GFR <>50% stenosis (CT angio, MRA or digital subtraction angiography) with in 1 cm of the origin of the renal artery. They also excluded patients with uncontrolled blood pressure (>140/90) this was done because if patients randomized to medical management developed uncontrollable blood pressure they could cross over and receive a stent.
The end point was a persistant 20% reduction of GFR by Cockcroft-Gault for more than a month.
Results: No significant difference between the two treatment strategies.
The Kaplan-Meier curves confirm this. The top graph is the primary outcome and the bottom graph is primary outcome plus death:
Renal angioplasty resulted a variety of complications:
Two patients in the stent group died of procedure-related causes within 30 days after stent placement. In 1 of the patients, embolization of a perforated renal artery was required; the patient subsequently developed pulmonary edema and needed mechanical ventilation, and died of a massive ischemic stroke 3 days later. The second patient had perforation of a renal artery branch; the artery was embolized, but despite re-intervention, the patient went into hypovolemic shock and experienced the acute respiratory distress syndrome, and died of multiorgan failure after 1 week.
The most common complications after stent placement were minor and mainly consisted of hematoma at the puncture site (11 patients [17%]). In 1 of these patients, secondary infection in the groin required surgical reconstruction. The patient thereafter developed end-stage renal failure, pulmonary edema, and heart failure and died 6 months after the procedure. In 2 other patients, stent placement was complicated by false aneurysm of the femoral artery. Injury to the kidney or renal artery occurred in 5 patients; however, this was never associated with loss of renal function and additional intervention was never required.
One patient in the stent group who had repeated angiography required permanent dialysis after cholesterol embolism.
So another negative trial of renal artery revascularization. We are still waiting for the publication of ASTRAL, a much larger and more definitive trial. CORAL is another trial which is ongoing and will shed further light on this subject.